PROJECT SUMMARY/ABSTRACT Project 1 - Clinical evolution and prognostic markers in patients with Chagas disease Although the natural history of Chagas disease (ChD) has been described decades ago, there are important gaps in the knowledge about the natural history. It is well known that after the acute phase, most patients enter the indeterminate form of the chronic phase. Each year, near 2% of them show evidence of involvement of the heart, what is called Chronic Chagas Cardiomyopathy (CCC), the most important clinical presentation of ChD. The clinical course of CCC is variable and identifying patients who are at risk of progressive CCC and death remains an unsolved challenge. This investigation aims to study the natural history of ChD in order to recognize prognostic markers related to risk of progression to cardiopathy and death. Considering the wide variability of ChD is important to know: a) What are the factors associated with the progression from the indeterminate form to the cardiac form? b) In patients with CCC, what are the factors associated with the increased risk of death and of development of severe cardiomyopathy? To answer these questions, we planning to establish a large prospective cohort including a total of 3,049 patients from two different NIH- sponsored studies as follow: 1) The Retrovirus Epidemiological Donor Study-II (REDS-II) and; 2) The Cardiomyopathy Cohort (SaMi-Trop Cohort). These will allow us to evaluate the prognostic value of the several markers tested at the time of the enrollment visit. For question 1 we propose to conduct a second visit to REDS-II. This project, conducted from 2008 to 2010, enrolled 499 T. cruzi seropositive donors identified through blood donor screening up to 10 years earlier, 488 matched seronegative donors from the same time period, and 101 symptomatic ChD patients. Blood donors were recruited from two Blood centers, one in Sao Paulo and another at Montes Claros, Minas Gerais State. These patients were submitted to a complete evaluation during the visit of 2008-2010 and most blood donors did not present cardiopathy. Thus, this is an ideal cohort to evaluate the progression from the indeterminate to the cardiac form. For question 2 we propose to conduct a third visit to SaMiTrop cohort. This cohort was based in a telehealth program designed to support primary care attention and included a total of 1,959 patients with CCC. The study is being conducted in 21 towns of the northern part of Minas Gerais state, and initially it was planned to have just one follow up visit. The baseline evaluation has been concluded in 2013 and 2014, and the follow up (2015-2016) is with 70% completed. With a second follow-up visit, it would be possible to further recognize prognostic markers, as well as test the clinical prediction rule developed during the first phase of the study.